Síntese e caracterização de complexos de prata(I) com ligantes quelantes doadores N,N, N,O e N,S: avaliação da citotoxicidade e atividade antibacteriana

Abstract

In this work, silver(I) complexes containing heterocyclic ligands from the phenanthroline and (thio)semicarbazone classes were synthesized and characterized to investigate their antitumor and antibacterial properties. The synthesis was carried out homogeneous conditions, yielding products with good yields (60–88%). The complexes were characterized by techniques including infrared spectroscopy (IR), UV-Vis spectroscopy, 1H and 13C NMR, elemental analysis (CHN), and high-resolution mass spectrometry (UHPLC-QTOF-MS). Cytotoxicity assays revealed significant activity of the complexes against tumor cell lines A2780, MDA-MB-231 and A549, with IC50 values ranging from 0.18 to 7.2 μM. Several complexes exhibited selectivity over the non-tumor cell line MRC-5, with selectivity indices (SI) greater than 5, particularly the [Ag(phendione)(scz)]⁺ complex. Additionally, the complexes showed selective inhibitory activity against topoisomerase IIα, without affecting the IIβ isoform, indicating potentially beneficial enzymatic selectivity. Assays performed with the pUC19 plasmid showed no significant DNA cleavage at the tested concentrations. Microbiological tests demonstrated antibacterial activity against Gram-positive strains (S. aureus, S. epidermidis) and Gram-negative strains(E. coli, K. pneumoniae). The [Ag(phendione)(scz)]⁺ complex stood out with minimum inhibitory concentrations (MIC) ranging from 1.95 to 15.6 μg mL-1. The greater susceptibility observed in Gram-positive bacteria may be attributed to the absence of the lipopolysaccharide outer membrane, facilitating access of the complexes to intracellular targets. Regarding anti-Leishmania activity (promastigotes), complexes containing phendiona or batophen exhibited submicromolar EC₅₀ values: 0.2–0.5 μM for L. amazonensis and 0.3 – 0.5 μM for L. braziliensis, with cytotoxicity in RAW 264.7 within 1.6 – 3.8 μM, resulting in selectivity indices (SI) frequently > 8 (up to ~12.7, depending on the system). Taken together, the results identify Ag(I) complexes with N,O/N,S-donor ligands as multifunctional candidates with relevant potency and selectivity, directed interaction with biomolecular targets (topo IIα), and broad activity spectrum (tumors, bacteria, and Leishmania), thereby justifying mechanistic studies and in vivo evaluation.